A broad research plan is proposed which is aimed at elucidating the nature of the protein-lipid interaction. A wide array of biophysical and chemical techniques will be brought to bear on the problem. Three large projects are proposed. C55-isoprenoid alcohol phosphokinase, purified in organic solvents from S. aureus H. membranes, is the most hydrophobic protein known. It is an intrinsic membrane protein which requires phospholipid for activity. A physical chemical approach is designed to define the nature of the phospholipid-kinase interaction, including optical methods, NMR, X-ray diffraction, and electron microscopy. Pyruvate Oxidase from E. coli is a water-soluble enzyme whose activity is markedly altered by phospholipids and fatty acids. Equilibrium dialysis will be used to define the number and nature of the lipid binding sites. Chemical methods, such as affinity labelling, are proposed to help isolate the peptide at the binding site. It is hoped that a simple system for studying the nature of the interaction between peptides and phospholipid liposomes can be developed. The aim is to dissect out the various forces contributing to and the structural requirements for the interaction. A long-term goal is the design of lipid sequestering proteins (artificial serum lipoproteins). Such peptides could conceivably be used to control or reverse lipid deposition in blood vessel walls. This would be very important to the treatment of atherosclerosis, heart disease, and stroke (infarctions).